OBJECTIVETo investigate the reversing effects of curcumin on hepatocellular carcinoma drug resistance Bel7402/5-Fu cell line.

METHODSThrough the exposure to gradual increased concentrations of 5-fluorouracil (5-Fu), the cell line Bel7402 was induced to establish a multi-drug resistant sub-cell line Bel7402/5-Fu. The sensitivity to 6 chemotherapeutics of Bel7402 and Bel7402/5-Fu were detected using methyl thiazolyl tetrazolium (MTT) assay. The 50% inhibitory concentration (IC50) and resistant index (RI) were calculated. The differences of the inhibition ratio of Bel7402/5-Fu by curcumin, 5-Fu, curcumin combined with 5-Fu were detected using MTT assay. The effects of curcumin, 5-Fu, curcumin combined with 5-Fu on the Bel7402/5-Fu apoptosis were detected using flow cytometry.

RESULTSThe Bel7402/5-Fu cell line showed multi-drug resistance (MDR) to various chemotherapeutics, with the highest RI shown of 5-Fu (being 109.55 +/- 14.30 times). The inhibition ratio of 5, 10, and 20 microg/mL curcumin combined with 5-Fu (50% IC50) was respectively 21.47% +/- 1.49%, 27.10% +/- 2.32%, and 59.37% +/- 2.45%. The Bel7402/5-Fu apoptosis ratio of 5, 10, and 20 microg/mL curcumin combined with 5-Fu (50% IC50) was 30.92% +/- 2.10%, 44.87% +/- 2.24%, and 50.36% +/- 2.58%, respectively, which was obviously higher than that of the curcumin group and the 5-Fu group. Besides, the apoptosis rate increased along with increased curcumin concentration in the range of 0 -20 microg/mL.

CONCLUSIONCurcumin could induce the apoptosis of Bel7402/5-Fu. Meanwhile, it showed favorable reversing effects on MDR.

Cell Line, Tumor ; Curcumin ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Fluorouracil ; pharmacology ; Humans

OBJECTIVETo study the preparation of recombinant house dust mite group 1 allergen vaccine (chitosan-pVAX1-Derp1 nanoparticles, pVAX1-Derp1/CS) and to investigate the efficacy and mechanism of intranasally given chitosan-pVAX1-Derp1 nanoparticles on mouse model with allergic rhinitis (AR).

METHODSThe chitosan-pVAX1-Derp1 nanoparticles was prepared by complex coacervation, and its nature was identified and analysed. A total of 40 BALB/c rats were randomly divided into 5 groups: the normal group (group A), the AR model group (group B), the chitosan (CS) prevention group (group C), the pVAX1-Derp1 prevention group (group D), and the pVAX1-Derp1/CS prevention group (group E). The nasal cavity of rats in the group B, C, D and E were dripped with phosphate buffered saline (20 µl), CS (20 µl), pVAX1-Der p1 (20 µl), pVAX1-Derp1/CS nanoparticles (20 µl) on the first day and day 8, once daily. Rats in the latter 4 group were sensitized with Der p1 and Al(OH)3 in day 15 and day 22, and challenged with Der p1 to establish AR model from day 36 to day 43, while rats in group A were treated with PBS. Then the level of cytokines in serum was assayed by ELISA, inflammatory reactions in nasal mucosa were analyzed by haematoxylin and eosin staining.

RESULTSpVAX1-Derp1/CS nanoparticles was successfully constructed, the mean grain size of pVAX1-Derp1/CS was (205.3 ± 12.8) nm, and the zeta potential was (30.5 ± 5.6) mV. In nasal mucosa tissue, group B and C showed significant allergic inflammation, while group D and E showed lighter allergic inflammation. Compared with the group B, the group D and E could effectively reduced serum IgE level and IL-4 level [group B: (120.0 ± 8.8) ng/ml, (248.7 ± 10.6) pg/ml; group D: (109.6 ± 14.5) ng/ml, (192.5 ± 10.2) pg/ml; group E: (88.1 ± 8.3) ng/ml, (165.7 ± 9.7) pg/ml; IgE: t value were 3.5, 6.9, all P < 0.01; IL-4: t value were 10.0, 15.2, all P < 0.01], and increased IFN-γ level [group B: (709.0 ± 26.5) pg/ml; group D: (856.3 ± 37.4) pg/ml; group E: (904.8 ± 37.7) pg/ml; t value were 8.2, 10.8, all P < 0.01)]. IL-10 level of group D [(129.9 ± 16.1) pg/ml] and E [(107.1 ± 11.8) pg/ml] was lower than IL-10 level of group B [(160.6 ± 24.2) pg/ml]. The difference were significantly (t value were 2.9, 5.5, all P < 0.05).

CONCLUSIONSChitosan can effectively encapsulate pVAX1-Derp 1 and inhibit nuclease degradation of the plasmid, the DNA vaccine has some preventive effect on AR animal model by nasal immunization.

Administration, Intranasal ; Animals ; Antigens, Dermatophagoides ; immunology ; Chitosan ; administration & dosage ; Cytokines ; blood ; Immunization ; methods ; Immunoglobulin E ; blood ; Mice ; Mice, Inbred BALB C ; Nanoparticles ; administration & dosage ; Nasal Mucosa ; immunology ; Plasmids ; Rhinitis, Allergic, Perennial ; prevention & control ; Vaccines, DNA ; genetics ; immunology

OBJECTIVETo study the expression of WAVE1 and p22phox in peripheral blood mononuclear cells (PBMCs) in children with acute lymphocytic leukemia (ALL) and the relationship of WAVE1 with oxidative stress.

METHODSReal-time PCR was used for detecting WAVE1 and p22phox expression in PBMCs in 41 children with ALL and 10 normal controls. Plasma activity of superoxide dismutase (SOD) was measured by the xanthine oxidase method. Plasma activity of GSH-Px was measured by the DTNB reaction test.

RESULTSThe expression of WAVE1 and p22phox was significantly higher in the active ALL groups (newly diagnosed and relapse ALL) than that in the normal control and the complete remission (CR) ALL groups (<0.01). The CR ALL group showed increased WAVE1 and p22phox expression than those in the normal control group (<0.05). Plasma activities of SOD (22.62+/-7.39 U/mL) and GSH-Px (91.73+/-28.88 micromol/L) in the active ALL group were significantly lower than those in the normal control (166.35+/-27.93 U/mL and 490.94+/-39.38 micromol/L, respectively) and the CR ALL groups (107.11+/-28.57 U/mL and 267.56+/-82.64 micromol/L, respectively) (<0.01). WAVE1 expression was positively correlated with p22phox expression (r=0.34, <0.05) but negatively correlated with plasma activities of SOD and GSH-Px ( r=-0.336 and-0.408, respectively; <0.05).

CONCLUSIONSWAVE1 and p22phox expression in PBMCs increased and was associated with the disease course in children with ALL. Oxidative stress may be involved in the regulation of WAVE1 expression in ALL children.

Adolescent ; Child ; Child, Preschool ; Female ; Glutathione Peroxidase ; blood ; Humans ; Infant ; Leukocytes, Mononuclear ; metabolism ; Male ; NADPH Oxidases ; genetics ; Oxidative Stress ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; RNA, Messenger ; blood ; Superoxide Dismutase ; blood ; Wiskott-Aldrich Syndrome Protein Family ; genetics

AIM:To observed the protective effect of diminazene aceturate(DIZE),an angiotensin-converting enzyme 2(ACE2)activator,on rats with diabetic cardiomyopathy(DCM).METHODS:Male Wistar rats(n=30)were randomly divided into normal control group ,DCM group and DIZE treatment group(DIZE group).The rats in DCM group and DIZE group were intraperitoneally injected with streptozotocin(65 mg/kg )to establish diabetic model.After 12 weeks,the diabetic rats were infused with DIZE at 15 mg· kg-1 · d-1 or the same volume of saline for 4 weeks using os-motic minipump.The cardiac function was measured at the end of the 16th week.The methods of Mason staining and HE staining were used to observe the morphological changes of the myocardial tissue.Western blot ,ELISA and immunohisto-chemistry were used to observe the changes of ACE2,angiotensin(Ang)Ⅱ,Ang-(1-7),interleukin(IL)-1,IL-6 and connective tissue growth factor(CTGF).RESULTS:DIZE significantly improved the expression of ACE 2 in diabetic rats(P<0.05).Compared with DCM group,the levels of IL-1 and IL-6 in DIZE group were significantly decreased ,and the cardiac function in DIZE group was significantly improved(P<0.05).CONCLUSION:ACE2 endogenous agonist DIZE significantly increases the ACE 2 level and reduces the level of inflammation ,thus protecting the heart function of DCM rats.

Adult ; Aged ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Case-Control Studies ; Cell Cycle Proteins ; metabolism ; Female ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Minichromosome Maintenance Complex Component 2 ; Nuclear Proteins ; metabolism

OBJECTIVETo identify epidemic status of murine typhus in Hongta areas of Yuxi city and to provide evidence for control and prevention of the disease.

METHODSSerologic survey was conducted among residents and rodents. Isolation of Rickettsia moseri was performed.

RESULTSThe overall infection rate among general population was 28.92% (96/332) with geometric meantiter (GMT) as 10.83 and there was no difference between males and females (26.71%, 43/161 vs. 30.99%, 53/171, P > 0.05). Significant differences were found between age groups (P < 0.05) with positive rates of 29.63% (8/27), 18.06% (13/72), 39.62% (42/106), 27.50% (22/80) and 23.40% (11/47) among age groups 0-6, 7-18, 19-39, 40-59 and over 60, respectively. The overall rate of infection in mouse was 44.95% (89/198) with GMT as 30.30. Five isolates of R. moseri from mouse specimen, three from fleas plus one case of murine typhus were diagnosed. Rattus norvegicus and Rattus flavipectus were the predominant species of rodent animals (99.49%, 197/198) and Xenopsylla cheopis was the major species of vector (74.26%, 303/408). Flea index and mouse density were 2.06 and 11.13% respectively.

CONCLUSIONHigh infection rates on R. moseri were demonstrated in rodents and residents as well as high risk of murine typhus outbreak might occur in these areas.

Adolescent ; Adult ; Animals ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Mice ; Middle Aged ; Rats ; Rodent Diseases ; epidemiology ; microbiology ; transmission ; Siphonaptera ; microbiology ; Typhus, Endemic Flea-Borne ; epidemiology ; microbiology ; transmission ; Young Adult

Objective: To analyze influencing factors for depressive symptoms in the elderly aged 65 years and older in 8 longevity areas in China. Methods: We recruited 2 180 participants aged 65 years and older in 8 longevity areas from Healthy Aging and Biomarkers Cohort Study, a sub-cohort of the Chinese Longitudinal Healthy Longevity Survey in 2017. Multivariate logistic regression analysis was performed to evaluate the relationships of socio-demographic characteristics, behavioral lifestyle, chronic disease prevalence, functional status, family and social support with depressive symptoms in the elderly. Results: The detection rate of depression symptoms was 15.0% in the elderly aged 65 years and older in 8 longevity areas of China, and the detection rate of depression symptoms was 11.5% in men and 18.5% in women. Multivariate logistic regression analysis results showed that the detection rate of depressive symptoms was lower in the elderly who had regular physical exercises (OR=0.44, 95%CI: 0.26-0.74), frequent fish intakes (OR=0.57, 95%CI: 0.39-0.83), recreational activities (OR=0.65, 95%CI: 0.44-0.96), social activities (OR=0.28, 95%CI: 0.11-0.73) and community services (OR=0.68, 95%CI: 0.50-0.93). The elderly who were lack of sleep (OR=2.04, 95%CI: 1.49-2.80), had visual impairment (OR=1.54, 95%CI: 1.08-2.18), had gastrointestinal ulcer (OR=2.97, 95%CI: 1.53-5.77), had arthritis (OR=2.63, 95%CI: 1.61-4.32), had higher family expenditure than income (OR=1.80, 95%CI: 1.17-2.78) and were in poor economic condition (OR=4.58, 95%CI: 2.48-8.47) had higher detection rate of depressive symptoms. Conclusion The status of doing physical exercise, fish intake in diet, social activity participation, sleep quality or vision, and the prevalence of gastrointestinal ulcers and arthritis were associated with the detection rate of depressive symptoms in the elderly.

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases